Our medical policies are designed for informational purposes only and are not an authorization, or an explanation of benefits, or a contract. Receipt of benefits is subject to satisfaction of all terms and conditions of the coverage. Medical technology is constantly changing, and we reserve the right to review and update our policies periodically.

Description

Parkinson's disease is a degenerative disease that includes symptoms of resting tremor, rigidity, and bradykinesia. The condition usually appears after age 40 years and progresses slowly over many years. Drug treatment with levodopa can usually restore smooth motor function for up to 5–10 years after onset of Parkinson's disease by permitting surviving dopaminergic cells to bypass a rate-limiting enzyme, tyrosine hydroxylase, and thus produce enough dopamine to maintain adequate motor function. Eventually, more dopaminergic cells die, leading to progressive disability.

In an effort to modify motor disability of advanced Parkinson's disease, embryonic mesencephalic (midbrain) tissue containing dopamine-producing cells is implanted into the caudate and putamen of the candidate's brain.

Policy

Fetal mesencephalic transplantation for the treatment of Parkinson’s disease is considered investigational.

Policy Guidelines

No applicable information

Benefit Application

Embryonic mesencephalic transplantation for the treatment of Parkinson’s disease is a specialized procedure that may require out of network referral.

Rationale

This policy is based on a 2001 TEC Assessment (1), which updated a prior 1995 TEC Assessment. (2). The 2001 TEC Assessment offered the following observations and conclusions:

Most of the studies published since the 1995 Assessment consist of uncontrolled open trials, examining clinical outcomes in small groups of patients. As such, they lack the strength conferred by study designs with control groups, randomization, and double-blinding protocol. However, these studies report minor to moderate improvement in motor function in at least some patients in each study. Magnitude of the treatment effect, however, is variable.

There has been 1 randomized controlled trial, reporting clinical outcomes for 33 patients. Clinical outcomes among these patients were variable, moderate in magnitude, and were in part affected by age. The primary outcome variable, a patient-scored global rating, showed no significant difference at 12 months after surgery between patients treated with transplantation and those undergoing sham surgery.

Because of the variability in the therapeutic effect of transplantation, particularly in patients older than 60 years of age, and the risk of severe dyskinesia and dystonia unresponsive to withdrawal of dopamine-agonist medication, the evidence is not sufficient to permit a conclusion that transplantation of embyronic dopamine neurons improves the net health outcomes for patients with advanced Parkinson's disease.

Another large, long-term randomized controlled study sponsored by the National Institutes of Health (NIH) was in progress for the 2001 TEC Assessment. However, results of this study were not available at that time.

A 2004 update of the peer-reviewed literature found publications on 2 randomized controlled trials (RCT) addressing health outcomes for Parkinson’s disease patients receiving embryonic mesencephalic transplantation. The publications identified included results from the completed NIH RCT referenced here (3) and an RCT sponsored by the National Institute of Neurological Disorders and Stroke (NINDS). (4-6) These studies do not alter the above conclusions.

In the NIH study, Olanow and colleagues reported on a double-blind, placebo-controlled trial of fetal nigral (the layer of gray substance separating the tegmentum of the midbrain from the crus cerebri) transplantation in 34 patients with advanced Parkinson's disease followed up prospectively for 24 months. (3) Patients were randomized to 1 of 4 donor bilateral transplantation or a placebo procedure. The authors reported no significant differences in overall treatment effect ( p = 0.244) and persistent dyskinesia in 56% of patients in the transplant group. While a treatment effect was seen in milder patients ( p = 0.006), the authors concluded the results did not support fetal nigral transplantation as a recommended therapy for Parkinson's disease.

In the NINDS double-blind, placebo-controlled RCT, 40 patients with Parkinson's disease were randomized to receive bilateral 4-donor implantation of embryonic mesencephalic cells or a placebo procedure and followed up for 1 year. Gordon et al reported patients in the NINDS trial improved significantly on reaction and movement times 12 months post-transplantation ( p = 0.005), while patients in the placebo group deteriorated. (4) The authors concluded reaction time analyses can be useful in identifying subtle motor performance changes over time.

McRae and colleagues reported on a portion of the NINDS RCT that evaluated quality of life (QOL) of 30 of the 40 study patients at baseline, 4, 8, and 12 months post-procedure. (5) The authors reported a strong placebo effect, since all patients reported better scores if they believed they had received the transplant.

Trott and colleagues reported on cognition 1 year post-procedure in the NINDS study. (6) The authors reported no significant differences in cognitive performance at follow-up for the transplant or placebo group as performance for most measures remained the same.